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Cerebral Cortex Advance Access published online on February 16, 2009
Cerebral Cortex, doi:10.1093/cercor/bhn256
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© The Author 2009. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

The Resting Brain: Unconstrained yet Reliable

Zarrar Shehzad1, A. M. Clare Kelly1, Philip T. Reiss2,3, Dylan G. Gee1, Kristin Gotimer1, Lucina Q. Uddin4, Sang Han Lee3, Daniel S. Margulies5, Amy Krain Roy1, Bharat B. Biswal3,6, Eva Petkova2,3, F. Xavier Castellanos1,3 and Michael P. Milham1

1 Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, NYU Child Study Center, New York, NY 10016, USA, 2 Division of Biostatistics, NYU Child Study Center, New York, NY 10016, USA, 3 Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA, 4 Department of Psychiatry, Stanford University School of Medicine, Stanford, CA, USA, 5 Berlin School for Mind and Brain, Humboldt Universitat, Berlin, Germany, 6 Department of Radiology, University of Medicine and Dentistry of New Jersey, Newark, NJ 07101, USA

Address correspondence to Dr Michael P. Milham, 215 Lexington Ave, 14th Floor, New York, NY 10016, USA. E-mail: milham01{at}med.nyu.edu.

Recent years have witnessed an upsurge in the usage of resting-state functional magnetic resonance imaging (fMRI) to examine functional connectivity (fcMRI), both in normal and pathological populations. Despite this increasing popularity, concerns about the psychologically unconstrained nature of the "resting-state" remain. Across studies, the patterns of functional connectivity detected are remarkably consistent. However, the test–retest reliability for measures of resting state fcMRI measures has not been determined. Here, we quantify the test–retest reliability, using resting scans from 26 participants at 3 different time points. Specifically, we assessed intersession (>5 months apart), intrasession (<1 h apart), and multiscan (across all 3 scans) reliability and consistency for both region-of-interest and voxel-wise analyses. For both approaches, we observed modest to high reliability across connections, dependent upon 3 predictive factors: 1) correlation significance (significantly nonzero > nonsignificant), 2) correlation valence (positive > negative), and 3) network membership (default mode > task positive network). Short- and long-term measures of the consistency of global connectivity patterns were highly robust. Finally, hierarchical clustering solutions were highly reproducible, both across participants and sessions. Our findings provide a solid foundation for continued examination of resting state fcMRI in typical and atypical populations.

Key Words: fMRI • intraclass correlations • reliability • resting-state functional connectivity • test–retest

Zarrar Shehzad and A. M. Clare Kelly contributed equally to the present work.


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